{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T19:36:23Z","timestamp":1791401783507,"version":"4.3.3"},"reference-count":23,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T00:00:00Z","timestamp":1767398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology Science Council, Republic of China","award":["NSTC 112-2320-B-002-030-MY2"],"award-info":[{"award-number":["NSTC 112-2320-B-002-030-MY2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dietary pattern characterized by low intake of vegetables and fruits and high consumption of fat, soft drink and desserts are associated with an increased risk of chronic diseases. To investigate the effects of folate status and fructose intake on adenine-induced chronic kidney disease (CKD), seven-week-old C57BL\/6 mice were divided into six groups and fed either a control diet (Ctrl), a 26% (w\/w) high-fructose diet (Hfru), Ctrl plus 0.15% adenine (Ctrl+ade), Hfru+ade, Hfru with folate deficiency plus adenine (Hfru\u2212f+ade), or Hfru with tenfold folate supplementation plus adenine (Hfru+f10+ade). After 10 weeks on the assigned diets, adenine was administrated to the +ade groups for 7 weeks. The results showed that all adenine-treated mice exhibited increased fasting blood glucose, urinary glucose, and elevated renal expression of collagen 1a1 (Col1a1), fibronectin (Fn1), and smooth muscle \u03b1-actin (Acta2). Compared with Ctrl mice, Hfru-fed mice showed significantly higher serum creatinine, increased urinary protein, and reduced creatinine clearance. Adenine induced kidney injury in all +ade groups, with the most severe damage observed in Hfru\u2212f+ade mice, as indicated by elevated blood urine nitrogen (BUN), urinary protein, neutrophil gelatinase-associated lipocalin (NGAL), and renal fibrosis. In contrast, Hfru+f10+ade mice showed the lowest levels of these renal injury markers. The Hfru+ade diets increased renal Hif1\u03b1 and iNos gene expression, which was further exacerbated by folate deficiency. Secretion of the anti-inflammatory cytokine interleukin (IL-10) by splenocytes was significantly reduced under folate-deficient conditions. Renal IL-10 levels were suppressed in all +ade groups but were significantly increased by folate supplementation. Renal IL-10 levels were negatively correlated with the inflammatory chemokine monocyte chemoattractant protein (MCP-1) and transforming growth factor (TGF)-\u03b2, whereas renal MCP-1 levels showed positive correlations with TGF-\u03b2 and IL-6. Overall, these findings suggest that high fructose consumption in the absence of adequate folate intake may be of concern for CKD progression.<\/jats:p>","DOI":"10.3390\/ijms27010499","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T12:38:56Z","timestamp":1767616736000},"page":"499","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effects of Folate and Fructose Intakes on Renal Cytokines and Fibrosis in an Adenine-Induced Mouse Model of Chronic Kidney Disease"],"prefix":"10.3390","volume":"27","author":[{"given":"Ting-Yu","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei 10617, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Ching","family":"Chiu","sequence":"additional","affiliation":[{"name":"Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei 10617, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bi-Fong","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei 10617, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kalmpourtzidou, A., Eilander, A., and Talsma, E.F. (2020). Global vegetable intake and supply compared to recommendations: A systematic review. Nutrients, 12.","DOI":"10.3390\/nu12061558"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Chan, C.W., and Lin, B.F. (2023). Folate deficiency enhanced inflammation and exacerbated renal fibrosis in high-fat high-fructose diet-fed mice. Nutrients, 15.","DOI":"10.3390\/nu15163616"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2336128","DOI":"10.1080\/0886022X.2024.2336128","article-title":"Adenine-induced animal model of chronic kidney disease: Current applications and future perspectives","volume":"46","author":"Yang","year":"2024","journal-title":"Ren. Fail."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1159\/000346180","article-title":"Development of a chronic kidney disease model in C57BL\/6 mice with relevance to human pathology","volume":"3","author":"Huang","year":"2013","journal-title":"Nephron Extra"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"French, B.W., Breidenbach, J.D., Yassine, S.G., Khatib-Shahidi, B.Z., Kazmi, S., Murphy, C.M., Bashir, H.S., Benson, E.M., Timalsina, B., and Shrestha, U. (2024). A simplified model of adenine-induced chronic kidney disease using SKH1 mice. Cells, 13.","DOI":"10.3390\/cells13242117"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"103419","DOI":"10.1016\/j.jff.2019.103419","article-title":"Gamma-aminobutyric acid decreases macrophages infiltration and suppresses inflammatory responses in renal injury","volume":"60","author":"Huang","year":"2019","journal-title":"J. Funct. Foods"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1152\/physiol.00046.2014","article-title":"Macrophages in kidney injury, inflammation, and fibrosis","volume":"30","author":"Cao","year":"2015","journal-title":"Physiology"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Prionas, A., Hamaoui, K., Vanezis, K., Reebye, V., Habib, N., and Papalois, V. (2024). The effect of interleukin-10 immunotherapy on renal ischemia-reperfusion injury: A systematic review and meta-analysis of preclinical studies. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25116231"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Liu, H., Li, Y., and Xiong, J. (2022). The role of hypoxia-inducible factor-1 alpha in renal disease. Molecules, 27.","DOI":"10.3390\/molecules27217318"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1111\/bph.14849","article-title":"Dual inhibition of cannabinoid CB1 receptor and inducible NOS attenuates obesity-induced chronic kidney disease","volume":"177","author":"Udi","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jnutbio.2016.11.008","article-title":"Folate deficiency affects dendritic cell function and subsequent T helper cell differentiation","volume":"41","author":"Wu","year":"2017","journal-title":"J. Nutr. Biochem."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Chan, C.W., Chan, P.H., and Lin, B.F. (2022). Folate deficiency increased lipid accumulation and leptin production of adipocytes. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.852451"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1093\/advances\/nmab049","article-title":"Ultra-processed foods and cardiovascular diseases: Potential mechanisms of action","volume":"12","author":"Juul","year":"2021","journal-title":"Adv. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1017\/S0007114521001665","article-title":"Relationship of several serum folate forms with kidney function and albuminuria: Cross-sectional data from the National Health and Nutrition Examination Surveys (NHANES) 2011\u20132018","volume":"127","author":"Liu","year":"2022","journal-title":"Br. J. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Pereira, R.M., Botezelli, J.D., da Cruz Rodrigues, K.C., Mekary, R.A., Cintra, D.E., Pauli, J.R., da Silva, A.S.R., Ropelle, E.R., and de Moura, L.P. (2017). Fructose consumption in the development of obesity and the effects of different protocols of physical exercise on the hepatic metabolism. Nutrients, 9.","DOI":"10.3390\/nu9040405"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1038\/s42255-024-01106-8","article-title":"On the pathogenesis of obesity: Causal models and missing pieces of the puzzle","volume":"6","author":"Magkos","year":"2024","journal-title":"Nat. Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1152\/physrev.00019.2009","article-title":"Metabolic effects of fructose and the worldwide increase in obesity","volume":"90","author":"Tappy","year":"2010","journal-title":"Physiol. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Jia, T., Olauson, H., Lindberg, K., Amin, R., Edvardsson, K., Lindholm, B., Andersson, G., Wernerson, A., Sabbagh, Y., and Schiavi, S. (2013). A novel model of adenine-induced tubulointerstitial nephropathy in mice. BMC Nephrol., 14.","DOI":"10.1186\/1471-2369-14-116"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"166825","DOI":"10.1016\/j.bbadis.2023.166825","article-title":"2,8-Dihydroxyadenine-induced nephropathy causes hexosylceramide accumulation with increased mTOR signaling, reduced levels of protective SirT3 expression and impaired renal mitochondrial function","volume":"1870","author":"Moellmann","year":"2024","journal-title":"BBA-Mol. Basis Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1007\/s00467-017-3774-5","article-title":"A review of the role of immune cells in acute kidney injury","volume":"33","author":"Bonavia","year":"2018","journal-title":"Pediatr. Nephrol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3186","DOI":"10.4049\/jimmunol.173.5.3186","article-title":"Folate deficiency reduces lymphocyte proliferation of primary human CD8+ T cells in vitro","volume":"173","author":"Courtemanche","year":"2004","journal-title":"J. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1007\/s12199-012-0286-6","article-title":"Folate-deficiency induced cell-specific changes in the distribution of lymphocytes and granulocytes in rats","volume":"18","author":"Abe","year":"2013","journal-title":"Environ. Health Prev. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"838S","DOI":"10.1093\/jn\/127.5.838S","article-title":"Components of the AIN-93 diets as improvements in the AIN-76A diet","volume":"127","author":"Reeves","year":"1997","journal-title":"J. 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